Background Meteorological factors are among the key extrinsic triggers for the onset and exacerbation of cardiovascular and cerebrovascular diseases (CVD). Against the backdrop of sustained global warming, elucidating the impact of ambient temperature and atmospheric pressure on CVD, especially on pre-hospital CVD emergent events, has become imperative for evidence-based prevention and emergency preparedness. Objective To quantify the temporal trends of daily mean temperature and atmospheric pressure and their associations with pre-hospital CVD emergent events in Yantai, and to explore effect modification by demographic subgroups and geographic areas, thereby providing an empirical basis for the rational allocation of emergency medical resources. Methods Pre-hospital CVD emergency data from January 1, 2016 to December 31, 2022 were selected from the Yantai 120 Emergency Medical Command System. Synchronous meteorological factors and environmental pollutant data were obtained from the websites of the National Oceanic and Atmospheric Administration and the National Centers for Environmental Information of the United States. Time-series analysis combined with distributed lag non-linear model was used to analyze the association between daily temperature, atmospheric pressure, and pre-hospital CVD emergencies. Average annual percentage changes (AAPC) were calculated using Joinpoint (version 5.2.0.0) to reflect temporal trends. Spearman correlation analysis was employed to screen variables with low collinearity for inclusion in the multi-pollutant adjusted models. Results From 2016 to 2022, a total of 268275 pre-hospital CVD emergency cases were recorded in Yantai City, showing an increasing annual trend (AAPC=7.16%, P=0.002). Emergency volume, daily temperature, atmospheric pressure, and PM₁₀ displayed marked seasonal patterns, with summer bottoms and winter peaks for emergencies, daily temperature higher in summer and lower in winter, and the inverse for atmospheric pressure. Correlation analysis showed that both daily temperature and atmospheric pressure were positively correlated with O₃, with correlation coefficients of 0.745 and 0.723, respectively; negatively correlated with PM_2.5, with correlation coefficients of −0.246 and −0.235, respectively; and negatively correlated with PM₁₀, with correlation coefficients of −0.241 and −0.229, respectively (P < 0.05). A U-shaped correlation was revealed between daily temperature and pre-hospital CVD emergency risk. Using 24 °C as the reference, risk was elevated at both low and high daily temperatures, with the strongest cold effect at –11 ℃ (RR=1.53, 95%CI: 1.35, 1.73) and strongest heat effect at 30 ℃ (RR=1.06, 95%CI: 1.01, 1.11); cold effects were prolonged (lag0–14d) compared to heat effects. Atmospheric pressure exhibited a positive association with emergencies; using a median of 1012.2 hPa as the reference, the maximum risk occurred at 1037 hPa (RR=1.25, 95%CI: 1.03, 1.52), with a 0–5 d lag. In the subgroup analysis, the impact of low temperature was more pronounced among females (RR_{−9 ℃}=1.66), people over 60 years (RR_{−9 ℃}=1.91), and rural residents (RR_{−9 ℃}=1.76). High atmospheric pressure significantly increased the risk of pre-hospital CVD emergency among females (RR_{1035 hPa}=1.54), people under 18 years (RR_{1035 hPa}=3.62), and rural residents (RR_{1035 hPa}=1.46). The sensitivity analysis results indicated that, after excluding the impact of pandemic and the degrees of freedom for time variations, the effects of daily average temperature and atmospheric pressure on pre-hospital CVD emergency volume were consistent with the primary analysis findings. Conclusion Both non-optimal temperature and atmospheric pressure significantly increase the pre-hospital CVD emergency volume; therefore, emergency medical services should develop targeted response protocols, optimize resource allocation, and intensify public health education to mitigate the pre-hospital burden attributable to temperature and pressure fluctuations.

ObjectiveTo establish the mouse models of psoriasis-like lesions induced by continuous cold exposure or intermittent cold exposure combined with imiquimod （IMQ）， and to evaluate the interventional effects of Kaixuan Jiedu core prescription （KXJD） on the two models. MethodsMale C57BL/6J mice were selected and classified into two experimental batches. The first batch of 36 mice was randomized into a room temperature group， a continuous cold exposure （10 ℃/24 h） group， and an intermittent cold exposure （10 ℃/6 h） group. Each group was further divided into a normal subgroup and a model subgroup （topical application of IMQ to induce skin lesions）， with 6 mice in each subgroup， for modeling and evaluation. The second batch of 54 mice， with 6 in each group， were subjected to the same temperature grouping with an additional KXJD （30.42 g·kg^-1， continuous gavage for 5 days） group. Comprehensive evaluation of model characteristics and KXJD efficacy was conducted through Psoriasis Area and Severity Index （PASI） scoring， skin temperature measurement by infrared thermography， histopathological observation by hematoxylin-eosin （HE） staining， detection of vascular endothelial growth factor （VEGF） and platelet endothelial cell adhesion molecule 1 （CD31） by immunohistochemistry， detection of Claudin-1 and Occludin by immunofluorescence assay， determination of serum levels of tumor necrosis factor-α （TNF-α） and interleukin （IL）-10 by enzyme-linked immunosorbent assay （ELISA）， and quantification of mRNA levels of IL-17A， IL-23， IL-6， and chemokine ligand 20 （CCL20） in skin lesions by quantitative Real-time polymerase chain reaction （Real-time PCR）. ResultsModel mice in all temperature groups exhibited typical psoriasis-like skin lesions. Compared with the normal groups， the model groups showed increased PASI scores， decreased skin temperatures （P<0.05）， obvious epidermal thickening， parakeratosis， and dermal inflammatory cell infiltration， as well as elevated mRNA levels of IL-17A， IL-23， IL-6， and CCL20 （P<0.05）. Cold exposure further aggravated psoriasis. The total PASI score of the intermittent cold exposure model group was higher than that of the room temperature model group （P<0.05）. The serum IL-10 did not show a compensatory elevation， and the blood vessels presented a characteristic of elevated CD31 expression （P<0.05） without a synchronous increase in VEGF. The continuous cold exposure model group exhibited more significant dermal capillary tortuosity and dilation， with the highest mRNA levels of IL-17A， IL-23， IL-6， and CCL20 among all groups. Compared with the respective model groups， KXJD intervention alleviated skin lesions， reduced epidermal thickness and inflammatory cell infiltration， and increased skin temperature， with the temperature increase being particularly significant in the intermittent cold exposure+KXJD group （P<0.05）. Furthermore， KXJD down-regulated the expression of VEGF and CD31， restored the expression of Claudin-1 and Occludin， decreased the mRNA levels of IL-17A and IL-23 （P<0.05）， and reduced the serum TNF-α level. ConclusionThis study successfully established compound psoriasis-like mouse models induced by cold exposure combined with IMQ. It confirms that cold aggravates the severity of psoriasis by exacerbating the closure of Xuanfu （sweat pores）， microcirculation disorders， and immune imbalance. Moreover， different cold exposure patterns have distinct mechanism differences. Continuous cold exposure focuses on enhancing the inflammatory response via the IL-23/IL-17 axis and angiogenesis， simulating chronic aggravation under a long-term cold environment. Intermittent cold exposure tends to impair immune regulation and induce microvascular endothelial stress， corresponding to acute exacerbations caused by sudden temperature drops. KXJD can effectively alleviate psoriasis-like skin lesions under cold conditions by unblocking Xuanfu， regulating vasomotor function， and correcting abnormal immune-inflammatory responses.

ObjectiveTo investigate the ameliorative effect and potential mechanisms of Kaixuan Jiedu core prescription （KXJD） on imiquimod （IMQ）-combined restraint stress-induced psoriasis-like skin lesions in mice. MethodsA total of 36 C57BL/6J mice were randomly assigned to six groups （n=6 per group）： Normal group， restraint stress blank group， model group， restraint stress model group， KXJD group （30.42 g·kg^-1）， and methotrexate group （0.001 g·kg^-1）. Psoriasis-like lesions were induced by topical IMQ application combined with restraint stress. After 5 days of intervention， the severity of skin lesions was evaluated using the Psoriasis Area and Severity Index （PASI）. The following parameters were assessed： Hypothalamic-pituitary-adrenal （HPA） axis-related hormones， including adrenocorticotropic hormone （ACTH）， corticotropin-releasing hormone （CRH）， and corticosterone （CORT）， central neuronal markers， including neuronal nuclei antigen （NeuN）， microtubule-associated protein 2 （MAP2）， and beta Ⅲ-tubulin （β-Ⅲ tubulin）， microglial activation markers， including ionized calcium-binding adapter molecule-1 （Iba-1） and cluster of differentiation 11b （CD11b）， and skin nerve fiber markers， including protein gene product 9.5 （PGP9.5） and serotonin （5-HT）， as well as the expression levels of inflammatory cytokines tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and interleukin-1 beta （IL-1β）. ResultsCompared with the normal group， both the model group and the restraint stress model group exhibited more severe psoriasis-like skin lesions， with significantly elevated serum levels of ACTH， CRH， and CORT （P<0.01）. The expression of glucocorticoid receptor （GR） and corticotropin-releasing hormone receptor 1 （CRHR1） in the skin was significantly downregulated. The expression of NeuN， MAP2， β-Ⅲ tubulin， Iba-1， and CD11b in the hypothalamus and hippocampus was significantly upregulated， suggesting abnormal changes in neuronal number or structure and aberrant activation of glial cells （P<0.05， P<0.01）. In addition， the expression of PGP9.5 and 5-HT in the skin， as well as the mRNA levels of TNF-α， IL-6， and IL-1β were all markedly elevated （P<0.05， P<0.01）. Compared with the model group， the restraint stress model group showed further exacerbation in most parameters. Compared with the restraint stress model group， the KXJD group exhibited significantly reduced PASI scores （P<0.01）， significantly decreased serum CRH， ACTH， and CORT levels （P<0.05， P<0.01）， upregulated skin GR and CRHR1 expression， inhibited abnormal neuronal changes and microglial activation in the hypothalamus and hippocampus， attenuated skin nerve fiber hyperplasia and amine signaling molecule release， and significantly reduced pro-inflammatory cytokine mRNA expression （P<0.05， P<0.01）. ConclusionKaixuan Jiedu Core prescription can effectively ameliorate IMQ combined with restraint stress-induced psoriasis-like skin lesions in mice by modulating HPA axis function， inhibiting central neuropathological changes， and attenuating skin nerve fiber hyperplasia， amine signaling molecule （5‑HT） release and local inflammatory responses.

Objective:To investigate the anti-inflammatory action and mechanism of action of rosmarinic acid(RA),a Chi-nese monomeric herbal compound based on the NF-κB/NLRP3 pathway in a rat model of acute gouty arthritis(AGA).Methods:Forty healthy male SD rats were randomly assigned to five groups,and the model and drug administration groups were established a rat model of AGA by injecting a suspension of sodium urate crystals(MSU)into the joint cavity of the right paw of the rats.The degree of ankle joint swelling was measured using vernier calipers and stained with hematoxylin-eosin(HE).The inflammatory infiltration of the ankle joint and chondrocyte shedding was observed by staining with Safranine O-fast green(SOFG)and Mankin's score.The levels of IL-6,IL-1β and TNF-α in the right ankle joint of rats were determined by ELISA and the expression of NF-κB/NLRP3 pathway-associated proteins in the ankle joint were measured by Western blot.Results:Injection of MSU suspension into the ankle successfully induced AGA in rats.Compared with control group,the rats in model group showed significantly increased ankle swelling(P<0.01),greater in-flammatory infiltration,significant chondrocyte detachment,significantly increased secretion of IL-1β,IL-6 and TNF-α(P<0.01)and increased expressions of NF-κB/NLRP3 pathway-related proteins.Compared with model group,RA showed greater anti-inflamma-tory effects,dose-dependently inhibiting the development of ankle swelling in rats(P<0.01,P<0.001)and inhibited inflammatory cy-tokine infiltration.RA inhibited the secretion of inflammatory cytokines IL-6,IL-1β,TNF-α(P<0.01)and inhibited the expressions of proteins associated with the NF-κB/NLRP3 pathway(P<0.01).Conclusion:RA shows potent anti-inflammatory effects in a mouse model of AGA,and the mechanism is associated with regulation of the NF-κB/NLRP3 pathway.

Objective To investigate the radiological features of intracranial white epidermoid cysts(WECs).Methods A retro-spective analysis was conducted on the CT and MRI findings of 7 patients pathologically confirmed with WECs.All patients under-went plain CT and MRI scans,and six patients underwent enhanced MRI scans.Results All cases were solitary lesions,located in the right middle cranial fossa(2 cases),suprasellar area(2 cases),left cerebellopontine angle(1 case),right cerebellar vermis(1 case),and cerebellomedullary cistern(1 case),respectively.The lesions appeared oval or irregular in shape with clear boundaries and no perile-sional edema.The CT scans predominantly showed high density in 7 cases,with calcification in 1 case.On T1WI,7 cases exhibited high signal with mixed signals in some areas;6 cases showed primarily low signal on T2WI and fluid attenuated inversion recovery(FLAIR),with 1 case predominantly showed high signal;all 7 cases demonstrated low signal on diffusion weighted imaging(DWI).The margins of 1 lesion appeared"curly",and another exhibited a"swirl"pattern.5 cases had no enhancement,while 1 case had mild marginal enhancement.Conclusion Intracranial WECs has certain imaging characteristics.When a cystic lesion shows high density on CT,predominantly high signal on T1WI,and mostly no enhancement,considering the possibility of WECs.

Objective To explore the functions of β-glucan-induced extracellular vesicles(EVs)released from J774A.1 cells.Methods EVs were extracted from the culture supernatant of J774A.1 cells,which were cultured with or without β-glucan,using differential centrifugation.The phenotype of extracellular vesicles was identified by transmission electron microscopy(TEM),nano-particle tracking analysis(NTA)and Western blotting(WB).The peritoneal macrophages(PMs)were harvested from C57BL/6J mice,and incubated with the control EVs(C-EVs)and theβ-glucan-induced EVs(G-EVs).Total RNA was extracted from the PMs and reversely transcribed to cDNA.The expression levels of the macrophage polarization-related genes were detected through real-time fluorescence quantitative PCR(qRT-PCR).Meanwhile,the culture supernatant of the PMs was collected and assayed by enzyme-linked immunosorbent assay(ELISA)to detect the expression levels of proinflammatory cytokines tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Results EVs of the control(C-EVs)and those from the β-glucan-induced(G-EVs)were isolated from J774A.1 cell culture medium.The results of TEM analysis showed that EVs had a membrane wrapped structure and the particle diameters ranged from 100 to 1000 nm.The NTA results showed that the average particle sizes were 162.4 and 175.6 nm respectively.The results of WB assay showed the expressions of characterized marker molecules such as CD81,CD9,CD63 and TSG101 were detected.qRT-PCR results showed that the expression levels of M1 polarization related genes such as Tnfa and inos were significantly increased in PM cells of the C-EVs treatment group,but those in the G-EVs treatment group were significantly lower than in the C-EVs treatment group.Meanwhile,the expression levels of M2 polarization indicators Cd206 and Arg-1 in the C-EVs treatment group were significantly decreased,while those in the G-EVs treatment group were significantly higher than those in C-EVs treatment group.Accordingly,the results of ELISA showed that the expression levels of TNF-α and IL-6 in the conditioned medium of the C-EVs treatment group were significantly increased,while those in the G-EVs treatment group were significantly lower than in the C-EVs treatment group.Conclusion Compared with the natural EVs from J774A.1 cells,the ability of β-glucan-induced EVs to drive M1 polarization of macrophages isdramatically compromised,with much fewer proinflammatory cytokines released,suggesting that β-glucan might contribute to immune regulation through EVs.

Purpose To investigate the expression of semaphorin 5 A(SEMA5A)and programmed death ligand-1(PD-L1)and their clinicopathological significance in gastric cancer.Methods Clinical data of 41 cases of gastric cancer tissues and paired adjacent tissues were collected.Immunohistochemical staining and RT-qPCR were used to de-tect the expression levels of SEMA5A and PD-L1,and analysed the correlation between SEMA5A and PD-L1 and clini-copathological features.In addition,we used lentivirus to construct SEMA5A stable low-expression cell lines.RT-qPCR and Western blot were used to analyse the correlation between the expression of SEMA5A and PD-L1 in gastric cancer tissues.Results The high expression rate of SEMA5A was 65.9％(27/41)in gastric cancer tissues and 39.0％(16/41)in paracancerous tissues,respectively.The positive rates of PD-L1 were 58.5％(24/41)and 14.6％(6/41),respectively.RT-qPCR showed that the relative expression levels of SEMA5A mRNA in gastric cancer and paracancerous tissues were 1.30±0.50 and 0.81±0.48,respectively,while the relative expression levels of PD-L1 mRNA were 0.70±0.42 and 0.12±0.09,respectively.SEMA5A expression was correlated with histological typ-ing of gastric cancer and lymph node metastasis(P＜0.05).PD-L1 expression was correlated with tumour size,T stage,and pathological stage of gastric cancer(P＜0.05).Pearson correlation analysis showed a positive correlation between the expression of SEMA5A and PD-L1 mRNA in gastric cancer tissues,and spearman correlation analysis showed that there was no correlation between the expression of the two in paracancerous tissues.Knockdown of SE-MA5A gene in human gastric adenocarcinoma cell lines resulted in down-regulation of PD-L1 expression.Conclusion Both SEMA5A and PD-L1 are highly expressed in gastric cancer tissues,and there is a correlation between the ex-pressions of SEMA5A and PD-L1.They can serve as potential molecular markers for prognostic evaluation and combi-nation therapy of gastric cancer.

Purpose To investigate the expression of semaphorin 5 A(SEMA5A)and programmed death ligand-1(PD-L1)and their clinicopathological significance in gastric cancer.Methods Clinical data of 41 cases of gastric cancer tissues and paired adjacent tissues were collected.Immunohistochemical staining and RT-qPCR were used to de-tect the expression levels of SEMA5A and PD-L1,and analysed the correlation between SEMA5A and PD-L1 and clini-copathological features.In addition,we used lentivirus to construct SEMA5A stable low-expression cell lines.RT-qPCR and Western blot were used to analyse the correlation between the expression of SEMA5A and PD-L1 in gastric cancer tissues.Results The high expression rate of SEMA5A was 65.9％(27/41)in gastric cancer tissues and 39.0％(16/41)in paracancerous tissues,respectively.The positive rates of PD-L1 were 58.5％(24/41)and 14.6％(6/41),respectively.RT-qPCR showed that the relative expression levels of SEMA5A mRNA in gastric cancer and paracancerous tissues were 1.30±0.50 and 0.81±0.48,respectively,while the relative expression levels of PD-L1 mRNA were 0.70±0.42 and 0.12±0.09,respectively.SEMA5A expression was correlated with histological typ-ing of gastric cancer and lymph node metastasis(P＜0.05).PD-L1 expression was correlated with tumour size,T stage,and pathological stage of gastric cancer(P＜0.05).Pearson correlation analysis showed a positive correlation between the expression of SEMA5A and PD-L1 mRNA in gastric cancer tissues,and spearman correlation analysis showed that there was no correlation between the expression of the two in paracancerous tissues.Knockdown of SE-MA5A gene in human gastric adenocarcinoma cell lines resulted in down-regulation of PD-L1 expression.Conclusion Both SEMA5A and PD-L1 are highly expressed in gastric cancer tissues,and there is a correlation between the ex-pressions of SEMA5A and PD-L1.They can serve as potential molecular markers for prognostic evaluation and combi-nation therapy of gastric cancer.

Objective To investigate the radiological features of intracranial white epidermoid cysts(WECs).Methods A retro-spective analysis was conducted on the CT and MRI findings of 7 patients pathologically confirmed with WECs.All patients under-went plain CT and MRI scans,and six patients underwent enhanced MRI scans.Results All cases were solitary lesions,located in the right middle cranial fossa(2 cases),suprasellar area(2 cases),left cerebellopontine angle(1 case),right cerebellar vermis(1 case),and cerebellomedullary cistern(1 case),respectively.The lesions appeared oval or irregular in shape with clear boundaries and no perile-sional edema.The CT scans predominantly showed high density in 7 cases,with calcification in 1 case.On T1WI,7 cases exhibited high signal with mixed signals in some areas;6 cases showed primarily low signal on T2WI and fluid attenuated inversion recovery(FLAIR),with 1 case predominantly showed high signal;all 7 cases demonstrated low signal on diffusion weighted imaging(DWI).The margins of 1 lesion appeared"curly",and another exhibited a"swirl"pattern.5 cases had no enhancement,while 1 case had mild marginal enhancement.Conclusion Intracranial WECs has certain imaging characteristics.When a cystic lesion shows high density on CT,predominantly high signal on T1WI,and mostly no enhancement,considering the possibility of WECs.

Objective:To investigate the anti-inflammatory action and mechanism of action of rosmarinic acid(RA),a Chi-nese monomeric herbal compound based on the NF-κB/NLRP3 pathway in a rat model of acute gouty arthritis(AGA).Methods:Forty healthy male SD rats were randomly assigned to five groups,and the model and drug administration groups were established a rat model of AGA by injecting a suspension of sodium urate crystals(MSU)into the joint cavity of the right paw of the rats.The degree of ankle joint swelling was measured using vernier calipers and stained with hematoxylin-eosin(HE).The inflammatory infiltration of the ankle joint and chondrocyte shedding was observed by staining with Safranine O-fast green(SOFG)and Mankin's score.The levels of IL-6,IL-1β and TNF-α in the right ankle joint of rats were determined by ELISA and the expression of NF-κB/NLRP3 pathway-associated proteins in the ankle joint were measured by Western blot.Results:Injection of MSU suspension into the ankle successfully induced AGA in rats.Compared with control group,the rats in model group showed significantly increased ankle swelling(P<0.01),greater in-flammatory infiltration,significant chondrocyte detachment,significantly increased secretion of IL-1β,IL-6 and TNF-α(P<0.01)and increased expressions of NF-κB/NLRP3 pathway-related proteins.Compared with model group,RA showed greater anti-inflamma-tory effects,dose-dependently inhibiting the development of ankle swelling in rats(P<0.01,P<0.001)and inhibited inflammatory cy-tokine infiltration.RA inhibited the secretion of inflammatory cytokines IL-6,IL-1β,TNF-α(P<0.01)and inhibited the expressions of proteins associated with the NF-κB/NLRP3 pathway(P<0.01).Conclusion:RA shows potent anti-inflammatory effects in a mouse model of AGA,and the mechanism is associated with regulation of the NF-κB/NLRP3 pathway.